Brain Surgery Without a Scalpel

The School of Medicine from the University of Virginia (UVA) researchers have developed a noninvasive way to remove faulty brain circuits that could allow doctors to treat debilitating neurological diseases without the need for conventional brain surgery. The UVA team, together with colleagues at Stanford University, indicate that the approach, if successfully translated to the operating room, could revolutionize the treatment of some of the most challenging and complex neurological diseases, including epilepsy, movement disorders and more. The approach uses low-intensity focused ultrasound waves combined with microbubbles to briefly penetrate the brain’s natural defenses and allow the targeted delivery of a neurotoxin. This neurotoxin kills the culprit brain cells while sparing other healthy cells and preserving the surrounding brain architecture.

A new alternative to brain surgery developed at UVA can wipe out out problematic neurons, a type of brain cell, without causing collateral damage.

This novel surgical strategy has the potential to supplant existing neurosurgical procedures used for the treatment of neurological disorders that don’t respond to medication,” said researcher Kevin S. Lee, PhD, of UVA’s Departments of Neuroscience and Neurosurgery and the Center for Brain Immunology and Glia (BIG). “This unique approach eliminates the diseased brain cells, spares adjacent healthy cells and achieves these outcomes without even having to cut into the scalp.”

The new approach is called PING, and it has already demonstrated exciting potential in laboratory studies. For instance, one of the promising applications for PING could be for the surgical treatment of epilepsies that do not respond to medication. Approximately a third of patients with epilepsy do not respond to anti-seizure drugs, and surgery can reduce or eliminate seizures for some of them. Lee and his team, along with their collaborators at Stanford, have shown that PING can reduce or eliminate seizures in two research models of epilepsy. The findings raise the possibility of treating epilepsy in a carefully-targeted and noninvasive manner without the need for traditional brain surgery.

Another important potential advantage of PING is that it could encourage the surgical treatment of appropriate patients with epilepsy who are reluctant to undergo conventional invasive or ablative surgery. In a scientific paper newly published in the Journal of Neurosurgery, Lee and his collaborators detail the ability of PING to focally eliminate neurons in a brain region, while sparing non-target cells in the same area. In contrast, currently available surgical approaches damage all cells in a treated brain region.

A key advantage of the approach is its incredible precision. PING harnesses the power of magnetic-resonance imaging (MRI) to let scientists peer inside the skull so that they can precisely guide sound waves to open the body’s natural blood-brain barrier exactly where needed. This barrier is designed to keep harmful cells and molecules out of the brain, but it also prevents the delivery of potentially beneficial treatments.

The UVA group’s new paper concludes that PING allows the delivery of a highly targeted neurotoxin, cleanly wiping out problematic neurons, a type of brain cell, without causing collateral damage.


Ultrasound Can Selectively Kill Cancer Cells

A new technique could offer a targeted approach to fighting cancer: low-intensity pulses of ultrasound have been shown to selectively kill cancer cells while leaving normal cells unharmed.

Ultrasound wavessound waves with frequencies higher than humans can hear—have been used as a cancer treatment before, albeit in a broad-brush approach: high-intensity bursts of ultrasound can heat up tissue, killing cancer and normal cells in a target area. Now, scientists and engineers are exploring the use of low-intensity pulsed ultrasound (LIPUS) in an effort to create a more selective treatment.

A study describing the effectiveness of the new approach in cell models was published in Applied Physics Letters. The researchers behind the work caution that it is still preliminary—it still has not been tested in a live animal let alone in a human, and there remain several key challenges to address—but the results so far are promising.

The research began five years ago when Caltech‘s Michael Ortiz, Frank and Ora Lee Marble Professor of Aeronautics and Mechanical Engineering, found himself pondering whether the physical differences between cancer cells and healthy cells—things like size, cell-wall thickness, and size of the organelles within them—might affect how they vibrate when bombarded with sound waves and how the vibrations might trigger cancer cell death.

I have my moments of inspiration,” Ortiz says wryly.

And so Ortiz built a mathematical model to see how cells would react to different frequencies and pulses of sound waves. Together with then-graduate student Stefanie Heyden (PhD ’14), who is now at ETH Zurich, Ortiz published a paper in 2016 in the Journal of the Mechanics and Physics of Solids showing that there was a gap in the so-called resonant growth rates of cancerous and healthy cells. That gap meant that a carefully tuned sound wave could, in theory, cause the cell membranes of cancerous cells to vibrate to the point that they ruptured while leaving healthy cells unharmed. Ortiz dubbed the process “oncotripsy” from the Greek oncos (for tumor) and tripsy (for breaking).